UNASSIGNED: In the battle against multidrug-resistant bacterial infections, ceftazidime- avibactam (CZA) stands as a pivotal defense, particularly against carbapenemresistant (CR) Gram-negative pathogens. However, the rise in resistance against this drug poses a significant threat to its effectiveness, highlighting the critical need for in-depth studies about its resistance mechanisms.
UNASSIGNED: This research focuses on the genomic characterization of CR- and CZA-resistant Escherichia coli (n=26) and Klebsiella pneumoniae (n=34) strains, harboring the blaNDM and/or blaOXA-48-like genes, at a major Lebanese tertiary care medical center, using whole genome sequencing (WGS).
UNASSIGNED: Our findings revealed a notable prevalence of blaNDM in all K. pneumoniae strains isolates, with 27 of these also harboring blaOXA-48. On the other hand, E. coli strains predominantly carried the blaNDM-5 gene. Whole genome sequencing (WGS) identified a predominance of ST383 among K. pneumoniae strains, which possessed a multi-replicon IncFIB-IncHI1B plasmid harboring the blaNDM-5. Additionally, various Inc group plasmids in K. pneumoniae across multiple sequence types were found to carry the blaNDM. Similarly, diverse STs of E. coli were observed to carry blaNDM-5 on different plasmids.
UNASSIGNED: The study underscores NDM carbapenemases as a paramount resistance mechanism in Lebanon,jeopardizing critical last-resort treatments. It also illuminates the role of varied sequence types and mobile genetic elements in the spread of NDM resistance,stressing the urgent need for strategies to mitigate this threat, especially in nosocomial infections.

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have been isolated from human patients in many countries across the globe but rarely in Saudi Arabia. Here we provide the genomic characterization of the first KPC-producing K. pneumoniae isolated from the urine of a patient in Riyadh, Saudi Arabia, who had a recent travel history to Egypt involving a medical procedure. Presence of KPC-encoding gene initially detected with the Xpert Carba-R assay was confirmed by traditional PCR. Susceptibility testing using the VITEK 2 system, E-test and microbroth dilution methods showed that the K. pneumoniae isolate, namely SA01_KPC-2, was resistant to all antibiotics except colistin and ceftazidime/avibactam. Whole-genome sequencing (WGS), performed on the Illumina Miseq instrument, identified the isolate as sequence type (ST) 383 and serotype KL30-D1 O1v2. Genome assembly of SA01_KPC-2 indicated the presence of two plasmids. Plasmid pSA01_KPC-2, of approximately 45.9 kb in size, harbored the blaKPC-2 flanked by ISKpn27 and ISKpn6 and had a backbone similar to published KPC-carrying IncX6 plasmids. The second plasmid pSA01_incHIB1, a derivative of published 372-kb plasmid pKpvST383, carried genes encoding virulence factors and resistance to five classes of antibiotics. The isolation of the first KPC producer in Saudi Arabia requires high attention and rapid interventions to prevent further spread.

BACKGROUND: The worldwide dissemination of the acquired carbapenemases in Gram-negative bacteria is a strongly expressed demand for the emergence of post antibiotic era. The aim of this study was to test the production of carbapenemase by Klebsiella pneumoniae strains isolated from hospitalized cancer patients and to investigate the genetic relationship of carbapenemase producing carbapenem resistant K. pneumoniae using multilocus sequence typing (MLST).
METHODS: Antibiotic susceptibility testing and phenotypic testing for extended spectrum b-lactamases (ESBL) and carbapenemases production were performed. PCR amplification of ESBL and carbapenemase genes was performed. MLST was done to detect the genetic relatedness of the isolates.
RESULTS: Our data showed all strains were sensitive to colistin. Carba NP test was positive in thirty-one carbapenem resistant K. pneumoniae isolates and 26 out of 34 K. pneumoniae isolates were metallo-beta-lactamases (MBL) positive. All carbapenemase-positive isolates were ESBL CTX-M-1-like positive. blaOXA-48 gene was detected in 25 isolates (80.65%) and 21 isolates (67.75%) produced blaNDM-1 like enzyme. VIM and KPC genes were not identified in this study. Association of blaOXA-48 like and blaNDM-1 like was found in 15 (48.39%) isolates, while the coproduction of OXA-48-like and IMP-1 was revealed in only one K. pneumoniae isolate. MLST revealed ten distinct sequence types (STs).
CONCLUSIONS: Here we have documented the coexistence of NDM-type and OXA-48-like, and the coproduction of OXA-48-like and IMP in carbapenem resistant K. pneumoniae in patients with cancer. The dominant clone of the OXA-48-like-producing K. pneumoniae isolates from Egypt was ST101 epidemic clone belonging to clonal complex 101, an association that has been reported worldwide. The second most frequent ST was ST383.ST11 was assigned to OXA-48-producing K. pneumoniae.